METABOLIC IMAGING OF MALIGNANT GLIOMA

恶性胶质瘤的代谢成像

• 批准号: 6236808
• 负责人: ALEXANDER M SPENCE
• 金额: $ 0.94万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-05-01 至 1998-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6236808
• 关键词: deoxyglucose; fluorine; glioma; glucose metabolism; human subject; human therapy evaluation; laboratory rat; neoplasm /cancer classification /staging; neoplasm /cancer diagnosis; neoplasm /cancer radiation therapy; neoplasm /cancer relapse /recurrence; pentose phosphate shunt; positron emission tomography; radionuclides; radiotracer

The overall goals of this research are to improve our understanding of how best to measure glucose metabolism (MRGlc) in malignant gliomas in vivo and to use such measurements for assessing the grade and distribution of malignancy within these tumors at initial presentation, after therapy and at recurrence. Monitoring the results of therapy, chiefly radiotherapy, with glucose metabolic measurements is aimed at defining when clinical benefit or failure has occurred and when radionecrosis has occurred. The readily available tracer, [F-18] fluorodeoxyglucose (FDG), with positron emission tomography (PET) will be evaluated for its utility and accuracy in the clinical management of malignant gliomas. To measure the MRGlc in gliomas with FDG accurately it is necessary to define specifically in the neoplastic tissue the uptake of FDG relative to glucose which includes transport from the plasma and subsequent phosphorylation by hexokinase to FDG-6-phosphate or glucose-6-phosphate respectively. This will be accomplished by dynamic PET studies that successively combine 1-[C-11]-glucose and FDG such that quantitative measurements of MRGlc with 1-[C-11]-glucose can be used to validate the results of FDG studies. Compartmental and distributed mathematical models designed for 1-[C-ll]-glucose and FDG individually will be used for this quantitative analysis. Also, biochemical measurements will be used to validate the PET measurements. For these, surgically removed human gliomas and normal human cortex, removed as part of surgery for intractable epilepsy, will be analyzed for the hexokinase kinetics of glucose and deoxyglucose and calculation of the phosphorylation ratio which defines the relative affinity of hexokinase for the two hexoses. The PET data gathered with 1-[C-11]-glucose will be used to test the hypothesis that there are diagnostic quantifiable patterns of tracer distribution and loss with 1-[C-11]-glucose in gliomas that are distinct from normal brain because of the combined effects of glycolysis to produce lactate and loss of the C1 carbon of glucose via the pentose shunt. The pentose shunt contribution to MRGlc in gliomas will be examined in PET studies that compare the kinetic behavior or 1-[C-11]- vs. 6-[C-11]-glucose. Studies in vitro of human and rat gliomas treated with either 1-[C-14]- or 6-[C-14]-glucose and studies in vivo in subcutaneously transplanted rat gliomas will augment the PET measurements. Lastly, we will test the hypotheses: (a) effective radiotherapy of malignant gliomas reduces the MRGlc sooner than CT or MRI changes indicate a therapeutic response and (b) pre- to immediate post-treatment reduction in MRGlc and immediate post-radiotherapy low tumor MRGlc both predict good therapy outcome. To do this we will image MRGlc before and within two weeks after radiotherapy, and at six months post-radiotherapy, and analyze these images in reference to time to tumor progression and length of survival.

这项研究的总体目标是提高我们对 如何在恶性神经胶质瘤中最好地测量葡萄糖代谢（MRGLC） 体内并使用此类测量来评估等级和 在初始介绍时，这些肿瘤内恶性肿瘤的分布， 治疗后和复发。 监测治疗结果， 主要是放疗，具有葡萄糖代谢测量的针对 定义何时发生临床利益或失败以及何时 发生了放射性症。 随时可用的示踪剂[F-18]氟脱氧葡萄糖（FDG），带有 正电子发射断层扫描（PET）将用于其效用和 恶性神经胶质瘤临床管理的准确性。 测量 精确的胶质瘤中的MRGLC准确地定义 特别是在肿瘤组织中 葡萄糖包括从血浆和随后的传输 己糖激酶磷酸化对FDG-6-磷酸或葡萄糖-6-磷酸盐的磷酸化 分别。 这将通过动态宠物研究来实现 依次结合1- [C-11] - 葡萄糖和FDG，以便定量 用1- [C-11] - 葡萄糖测量MRGLC可用于验证 FDG研究的结果。 隔室和分布式数学 为1- [C-LL] - 葡萄糖和FDG设计的模型将单独使用 对于此定量分析。 另外，生化测量将是 用于验证宠物测量值。 为此，手术删除 人神经胶质瘤和正常的人皮质，作为手术的一部分去除 将分析顽固性癫痫的己糖酶动力学 葡萄糖和脱氧葡萄糖以及磷酸化比的计算 定义了己糖酶对两个己糖的相对亲和力。 用1- [C-11] - 葡萄糖收集的PET数据将用于测试 假设有示踪剂的诊断量化模式 在神经胶质瘤中使用1- [C-11] - 葡萄糖的分布和损失，这是不同的 由于糖酵解的综合作用到正常的大脑 产生乳酸和通过五糖的C1碳的损失 分流。 戊糖分流对神经胶质瘤中MRGLC的贡献将为 在比较动力学行为或1- [C-11]的PET研究中检查了 vs. 6- [C-11] - 葡萄糖。 接受治疗的人类和大鼠神经胶质瘤的研究 用1- [C-14]或6- [C-14] - 葡萄糖和体内研究 皮下移植的大鼠神经胶质瘤将增强PET 测量。 最后，我们将测试假设：（a）有效的放疗 恶性神经胶质瘤比CT或MRI变化更快地减少MRGLC 表示治疗反应和（b）立即治疗 降低MRGLC和立即放射疗法的低肿瘤MRGLC均减少 预测良好的治疗结果。 为此，我们将在之前和 放疗后的两个星期，在放射治疗后六个月内， 并分析这些图像，以参考肿瘤进展的时间和 生存时间。